Evaluation of baculoviruses as gene therapy vectors for brain cancer
- Autores
- Garcia Fallit, Matías; Pidre, Matías Luis; Asad, Antonela S.; Peña Agudelo, Jorge A.; Vera, Mariana B.; Nicola Candia, Alejandro J.; Sagripanti, Sofia B.; Pérez Kuper, Melanie; Amorós Morales, Leslie Cinthya; Marchesini, Abril; Gonzalez, Nazareno; Caruso, Carla M.; Romanowski, Víctor; Seilicovich, Adriana; Videla Richardson, Guillermo A.; Zanetti, Flavia A.; Candolfi, Marianela
- Año de publicación
- 2023
- Idioma
- inglés
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- We aimed to assess the potential of baculoviral vectors (BV) for brain cancer gene therapy. We compared them with adenoviral vectors (AdV), which are used in neuro-oncology, but for which there is pre-existing immunity. We constructed BVs and AdVs encoding fluorescent reporter proteins and evaluated their transduction efficiency in glioma cells and astrocytes. Naïve and glioma-bearing mice were intracranially injected with BVs to assess transduction and neuropathology. Transgene expression was also assessed in the brain of BV-preimmunized mice. While the expression of BVs was weaker than AdVs in murine and human glioma cell lines, BV-mediated transgene expression in patient-derived glioma cells was similar to AdV-mediated transduction and showed strong correlation with clathrin expression, a protein that interacts with the baculovirus glycoprotein GP64, mediating BV endocytosis. BVs efficiently transduced normal and neoplastic astrocytes in vivo, without apparent neurotoxicity. BV-mediated transgene expression was stable for at least 21 days in the brain of naïve mice, but it was significantly reduced after 7 days in mice systemically preimmunized with BVs. Our findings indicate that BVs efficiently transduce glioma cells and astrocytes without apparent neurotoxicity. Since humans do not present pre-existing immunity against BVs, these vectors may constitute a valuable tool for the delivery of therapeutic genes into the brain.
Instituto de Biotecnología y Biología Molecular - Materia
-
Biología
Ciencias Médicas
Baculoviruses
Glioblastoma
Astrocytes
Gene therapy
Brain - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- http://creativecommons.org/licenses/by/4.0/
- Repositorio
- Institución
- Universidad Nacional de La Plata
- OAI Identificador
- oai:sedici.unlp.edu.ar:10915/152929
Ver los metadatos del registro completo
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Evaluation of baculoviruses as gene therapy vectors for brain cancerGarcia Fallit, MatíasPidre, Matías LuisAsad, Antonela S.Peña Agudelo, Jorge A.Vera, Mariana B.Nicola Candia, Alejandro J.Sagripanti, Sofia B.Pérez Kuper, MelanieAmorós Morales, Leslie CinthyaMarchesini, AbrilGonzalez, NazarenoCaruso, Carla M.Romanowski, VíctorSeilicovich, AdrianaVidela Richardson, Guillermo A.Zanetti, Flavia A.Candolfi, MarianelaBiologíaCiencias MédicasBaculovirusesGlioblastomaAstrocytesGene therapyBrainWe aimed to assess the potential of baculoviral vectors (BV) for brain cancer gene therapy. We compared them with adenoviral vectors (AdV), which are used in neuro-oncology, but for which there is pre-existing immunity. We constructed BVs and AdVs encoding fluorescent reporter proteins and evaluated their transduction efficiency in glioma cells and astrocytes. Naïve and glioma-bearing mice were intracranially injected with BVs to assess transduction and neuropathology. Transgene expression was also assessed in the brain of BV-preimmunized mice. While the expression of BVs was weaker than AdVs in murine and human glioma cell lines, BV-mediated transgene expression in patient-derived glioma cells was similar to AdV-mediated transduction and showed strong correlation with clathrin expression, a protein that interacts with the baculovirus glycoprotein GP64, mediating BV endocytosis. BVs efficiently transduced normal and neoplastic astrocytes in vivo, without apparent neurotoxicity. BV-mediated transgene expression was stable for at least 21 days in the brain of naïve mice, but it was significantly reduced after 7 days in mice systemically preimmunized with BVs. Our findings indicate that BVs efficiently transduce glioma cells and astrocytes without apparent neurotoxicity. Since humans do not present pre-existing immunity against BVs, these vectors may constitute a valuable tool for the delivery of therapeutic genes into the brain.Instituto de Biotecnología y Biología Molecular2023info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdfhttp://sedici.unlp.edu.ar/handle/10915/152929enginfo:eu-repo/semantics/altIdentifier/issn/1999-4915info:eu-repo/semantics/altIdentifier/doi/10.3390/v15030608info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/Creative Commons Attribution 4.0 International (CC BY 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-29T11:39:33Zoai:sedici.unlp.edu.ar:10915/152929Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:39:33.575SEDICI (UNLP) - Universidad Nacional de La Platafalse |
dc.title.none.fl_str_mv |
Evaluation of baculoviruses as gene therapy vectors for brain cancer |
title |
Evaluation of baculoviruses as gene therapy vectors for brain cancer |
spellingShingle |
Evaluation of baculoviruses as gene therapy vectors for brain cancer Garcia Fallit, Matías Biología Ciencias Médicas Baculoviruses Glioblastoma Astrocytes Gene therapy Brain |
title_short |
Evaluation of baculoviruses as gene therapy vectors for brain cancer |
title_full |
Evaluation of baculoviruses as gene therapy vectors for brain cancer |
title_fullStr |
Evaluation of baculoviruses as gene therapy vectors for brain cancer |
title_full_unstemmed |
Evaluation of baculoviruses as gene therapy vectors for brain cancer |
title_sort |
Evaluation of baculoviruses as gene therapy vectors for brain cancer |
dc.creator.none.fl_str_mv |
Garcia Fallit, Matías Pidre, Matías Luis Asad, Antonela S. Peña Agudelo, Jorge A. Vera, Mariana B. Nicola Candia, Alejandro J. Sagripanti, Sofia B. Pérez Kuper, Melanie Amorós Morales, Leslie Cinthya Marchesini, Abril Gonzalez, Nazareno Caruso, Carla M. Romanowski, Víctor Seilicovich, Adriana Videla Richardson, Guillermo A. Zanetti, Flavia A. Candolfi, Marianela |
author |
Garcia Fallit, Matías |
author_facet |
Garcia Fallit, Matías Pidre, Matías Luis Asad, Antonela S. Peña Agudelo, Jorge A. Vera, Mariana B. Nicola Candia, Alejandro J. Sagripanti, Sofia B. Pérez Kuper, Melanie Amorós Morales, Leslie Cinthya Marchesini, Abril Gonzalez, Nazareno Caruso, Carla M. Romanowski, Víctor Seilicovich, Adriana Videla Richardson, Guillermo A. Zanetti, Flavia A. Candolfi, Marianela |
author_role |
author |
author2 |
Pidre, Matías Luis Asad, Antonela S. Peña Agudelo, Jorge A. Vera, Mariana B. Nicola Candia, Alejandro J. Sagripanti, Sofia B. Pérez Kuper, Melanie Amorós Morales, Leslie Cinthya Marchesini, Abril Gonzalez, Nazareno Caruso, Carla M. Romanowski, Víctor Seilicovich, Adriana Videla Richardson, Guillermo A. Zanetti, Flavia A. Candolfi, Marianela |
author2_role |
author author author author author author author author author author author author author author author author |
dc.subject.none.fl_str_mv |
Biología Ciencias Médicas Baculoviruses Glioblastoma Astrocytes Gene therapy Brain |
topic |
Biología Ciencias Médicas Baculoviruses Glioblastoma Astrocytes Gene therapy Brain |
dc.description.none.fl_txt_mv |
We aimed to assess the potential of baculoviral vectors (BV) for brain cancer gene therapy. We compared them with adenoviral vectors (AdV), which are used in neuro-oncology, but for which there is pre-existing immunity. We constructed BVs and AdVs encoding fluorescent reporter proteins and evaluated their transduction efficiency in glioma cells and astrocytes. Naïve and glioma-bearing mice were intracranially injected with BVs to assess transduction and neuropathology. Transgene expression was also assessed in the brain of BV-preimmunized mice. While the expression of BVs was weaker than AdVs in murine and human glioma cell lines, BV-mediated transgene expression in patient-derived glioma cells was similar to AdV-mediated transduction and showed strong correlation with clathrin expression, a protein that interacts with the baculovirus glycoprotein GP64, mediating BV endocytosis. BVs efficiently transduced normal and neoplastic astrocytes in vivo, without apparent neurotoxicity. BV-mediated transgene expression was stable for at least 21 days in the brain of naïve mice, but it was significantly reduced after 7 days in mice systemically preimmunized with BVs. Our findings indicate that BVs efficiently transduce glioma cells and astrocytes without apparent neurotoxicity. Since humans do not present pre-existing immunity against BVs, these vectors may constitute a valuable tool for the delivery of therapeutic genes into the brain. Instituto de Biotecnología y Biología Molecular |
description |
We aimed to assess the potential of baculoviral vectors (BV) for brain cancer gene therapy. We compared them with adenoviral vectors (AdV), which are used in neuro-oncology, but for which there is pre-existing immunity. We constructed BVs and AdVs encoding fluorescent reporter proteins and evaluated their transduction efficiency in glioma cells and astrocytes. Naïve and glioma-bearing mice were intracranially injected with BVs to assess transduction and neuropathology. Transgene expression was also assessed in the brain of BV-preimmunized mice. While the expression of BVs was weaker than AdVs in murine and human glioma cell lines, BV-mediated transgene expression in patient-derived glioma cells was similar to AdV-mediated transduction and showed strong correlation with clathrin expression, a protein that interacts with the baculovirus glycoprotein GP64, mediating BV endocytosis. BVs efficiently transduced normal and neoplastic astrocytes in vivo, without apparent neurotoxicity. BV-mediated transgene expression was stable for at least 21 days in the brain of naïve mice, but it was significantly reduced after 7 days in mice systemically preimmunized with BVs. Our findings indicate that BVs efficiently transduce glioma cells and astrocytes without apparent neurotoxicity. Since humans do not present pre-existing immunity against BVs, these vectors may constitute a valuable tool for the delivery of therapeutic genes into the brain. |
publishDate |
2023 |
dc.date.none.fl_str_mv |
2023 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Articulo http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
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article |
status_str |
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dc.identifier.none.fl_str_mv |
http://sedici.unlp.edu.ar/handle/10915/152929 |
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http://sedici.unlp.edu.ar/handle/10915/152929 |
dc.language.none.fl_str_mv |
eng |
language |
eng |
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info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/4.0/ Creative Commons Attribution 4.0 International (CC BY 4.0) |
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openAccess |
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http://creativecommons.org/licenses/by/4.0/ Creative Commons Attribution 4.0 International (CC BY 4.0) |
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